Reppert Emily J, Kleinhenz Michael D, Montgomery Shawnee R, Heiman Jared, Sura Amanda, Bornheim Heather N, Magnin Geraldine, Sidhu Pritam K, Zhang Yuntao, Joo Hyun, Coetzee Johann F
Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas.
Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas.
J Vet Pharmacol Ther. 2019 Sep;42(5):572-579. doi: 10.1111/jvp.12800. Epub 2019 Jul 29.
The aim of this study was to determine the pharmacokinetics and prostaglandin E (PGE ) synthesis inhibiting effects of intravenous (IV) and transdermal (TD) flunixin meglumine in eight, adult, female, Huacaya alpacas. A dose of 2.2 mg/kg administered IV and 3.3 mg/kg administered TD using a cross-over design. Plasma flunixin concentrations were measured by LC-MS/MS. Prostaglandin E concentrations were determined using a commercially available ELISA. Pharmacokinetic (PK) analysis was performed using noncompartmental methods. Plasma PGE concentrations decreased after IV flunixin meglumine administration but there was minimal change after TD application. Mean t λz after IV administration was 4.531 hr (range 3.355 to 5.571 hr) resulting from a mean Vz of 570.6 ml/kg (range, 387.3 to 1,142 ml/kg) and plasma clearance of 87.26 ml kg hr (range, 55.45-179.3 ml kg hr ). The mean C T and t λz for flunixin following TD administration were 106.4 ng/ml (range, 56.98 to 168.6 ng/ml), 13.57 hr (range, 6.000-34.00 hr) and 24.06 hr (18.63 to 39.5 hr), respectively. The mean bioavailability for TD flunixin was calculated as 25.05%. The mean 80% inhibitory concentration (IC ) of PGE by flunixin meglumine was 0.23 µg/ml (range, 0.01 to 1.38 µg/ml). Poor bioavailability and poor suppression of PGE identified in this study indicate that TD flunixin meglumine administered at 3.3 mg/kg is not recommended for use in alpacas.
本研究的目的是确定静脉注射（IV）和透皮（TD）氟尼辛葡甲胺在8只成年雌性瓦卡亚羊驼体内的药代动力学及对前列腺素E（PGE）合成的抑制作用。采用交叉设计，静脉注射剂量为2.2mg/kg，透皮给药剂量为3.3mg/kg。通过液相色谱-串联质谱法（LC-MS/MS）测定血浆氟尼辛浓度。使用市售酶联免疫吸附测定法（ELISA）测定前列腺素E浓度。采用非房室方法进行药代动力学（PK）分析。静脉注射氟尼辛葡甲胺后血浆PGE浓度降低，但透皮给药后变化极小。静脉注射后的平均tλz为4.531小时（范围为3.355至5.571小时），这是由平均Vz为570.6ml/kg（范围为387.3至1142ml/kg）和血浆清除率为87.26ml·kg-1·hr-1（范围为55.45 - 179.3ml·kg-1·hr-1）导致产生的。透皮给药后氟尼辛的平均Cmax和tλz分别为106.4ng/ml（范围为56.98至168.6ng/ml）、13.57小时（范围为6.000 - 34.00小时）和24.06小时（18.63至39.5小时）。透皮氟尼辛的平均生物利用度计算为25.05%。氟尼辛葡甲胺对PGE的平均80%抑制浓度（IC80）为0.23μg/ml（范围为0.01至1.38μg/ml）。本研究中确定的生物利用度差和对PGE的抑制效果不佳表明，不建议以3.3mg/kg的剂量透皮给予氟尼辛葡甲胺用于羊驼。
